Taiho Oncology, Taiho Pharmaceutical and Cullinan Therapeutics have reported results from the Phase III REZILIENT3 trial, showing that zipalertinib combined with chemotherapy significantly improved progression-free survival (PFS) for patients with previously untreated, advanced non-small cell lung cancer (NSCLC).
The study focused on patients whose cancer was characterised by epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations.
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It enrolled 285 adults with locally advanced or metastatic, non-squamous NSCLC and EGFR ex20ins mutations.
These results were presented at the International Association for the Study of Lung Cancer’s (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea.
The randomised, open-label, multi-centre study assessed zipalertinib plus platinum-based chemotherapy compared to chemotherapy alone as first-line treatment.
The study met the primary endpoint of PFS, with patients receiving the combination showing a median PFS benefit of 6.0 months over chemotherapy alone.
Median PFS reached 14.5 months for the combination arm compared to 8.5 months for chemotherapy. The interim analysis was conducted after 122 events of PFS.
Objective response rates were also higher in those receiving zipalertinib with chemotherapy (65%) compared to chemotherapy alone (40.3%), and the median duration of response with the combination was 14.2 months versus 9.9 months.
At the interim overall survival analysis, conducted when 30% of events had occurred, the hazard ratio for death for the combination compared with chemotherapy alone was 0.72, with additional follow-up underway.
Taiho Pharmaceutical global chief medical officer Fabio Benedetti said: “We believe these results mark a potentially important step forward in the treatment of EGFR exon 20 insertion mutation-positive non-small cell lung cancer.
“To address the unmet medical needs of patients and their families, we will continue working closely with Taiho Oncology and Cullinan to make this treatment available to patients who may benefit from it.”
The adverse event profile of zipalertinib combined with chemotherapy was comparable to the known safety of the agents alone. Grade ≥3 adverse events were more frequent with the combination therapy (87.1% versus 54.4%), often involving haematological effects.
Grade ≥3 EGFR-related toxicities such as rash (10.7%) and diarrhoea (1.4%) only occurred in patients receiving the zipalertinib combination.
Zipalertinib (CLN-081/TAS6417) is an orally administered, investigational inhibitor targeting EGFR variants with ex20ins mutations and has not received approval from any health authority.
